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Bu X.,Early Development Analytical Research | Skrdla P.J.,Global Pharmaceutical Commercialization | Dormer P.G.,Process Research | Bereznitski Y.,Early Development Analytical Research
Journal of Chromatography A | Year: 2010

Analysis of atropisomers is of considerable interest in the pharmaceutical industry. For complex chiral molecules with several chiral centers hindered axial rotation can lead to formation of interconverting diastereomers that should be separable on achiral stationary phases. However, achieving the actual separation may be difficult as the on-column separation speed must match or be faster then the rate of isomer interconversion. Often, this requirement can be satisfied by using low-temperature conditions and by improving selectivity via use of chiral stationary phases. In the current study, we present an alternative approach utilizing an Obelisc R column, a novel mixed mode stationary phase that provided acceptable separation of triphenyl atropisomers inside a conventional HPLC temperature range. The separation was investigated under various chromatographic conditions. The interconversion chromatograms exhibited classic peak-plateau-peak behavior indicating the simultaneous atropisomer separation and interconversion. The elution profiles were integrated in order to deconvolute the peak areas of the " pure" (non-exchanged) and interconverted species; these data were used to obtain kinetic information. Analysis of retention data rendered thermodynamic information on the mechanism of retention and selectivity. Chromatographic kinetic data were complemented with variable-temperature NMR and molecular modeling studies, which provided additional support and insights into the energetics of the interconversion process. © 2010 Elsevier B.V. Source


Ramirez A.S.,University of Twente | Loendersloot R.,University of Twente | Tinga T.,University of Twente | D'Angelo G.,Process Research
Mechanisms and Machine Science | Year: 2015

Impact response due to sudden changes on the contact forces is an intrinsic phenomenon at all stages of the bearing life. Even prior to the actual occurrence of surface damage, short duration impacts occur in the case of insufficient lubrication where asperities or particles interact with the surface of its mating element. As the surface condition deteriorates, the energy released by the impacts increases affecting structural modes. As soon as the system condition worsens, lower frequencies are excited and consequently increased vibration levels are displayed. The impulse response function reflects the modulation phenomena between contact forces, structural resonances and driving forces taking place in the bearing and the mechanical system that contains it. The characterization of the components of the impulse response becomes then a valuable tool for vibration monitoring. This article is framed within the research on development of advanced vibration monitoring systems, for which the authors follow a systemic approach in the definition of the monitoring requirements based on the function-failure analysis of the monitored object. The discussion focuses on the correspondence between the monitoring and monitored systems, by analyzing the impulse beh avior as illustrated by the train bearings. The comparative analysis between environment and damage induced impacts highlights the different stages in bearing damage © Springer International Publishing Switzerland 2015. Source


Kallemeyn J.M.,Process Research | Ku Y.-Y.,Process Research | Mulhern M.M.,Process Research | Bishop R.,Process Research | And 2 more authors.
Organic Process Research and Development | Year: 2014

A scalable process for the preparation of 2-(2-(cis-3-(piperidin-1-yl) cyclobutyl)benzothiazol-6-yl)pyridazin- 3(2H)-one in multi-kilogram amounts and in high purity has been developed. The key features of this synthesis are the coppercatalyzed C-N cross-coupling reaction and the development of a highly diastereoselective reductive amination using NaBH(OPiv)3 as a reducing agent. Controls were implemented to minimize both base- and acid-catalyzed isomerization of the 1,3-cis-substituted cyclobutane ring. © 2013 American Chemical Society. Source

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